Content area
Full text
Received Oct 23, 2017; Revised Mar 25, 2018; Accepted Apr 19, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Hospital-acquired infections (HAIs) are considered one of the most frequent adverse events that threaten patients’ safety in healthcare settings throughout the world [1–3]. Critically ill patients in the intensive care unit (ICU) are extremely vulnerable to HAIs due to their severe illness status, malnutrition, increased invasive treatments, impaired immune function, and even the contaminated environment [3–5]. Currently, HAIs have become a serious issue in ICUs due to their high morbidity (nearly 15.1–47.9% all over the world), high mortality (27.6% or even higher), prolonged length of hospital stay, and increased economic burden [6], but there are no efficient tools for predicting HAIs. Studies show that among critically ill patients, the immune system undergoes simultaneous activation and suppression, leading to severe and persistent immune dysregulation [7, 8], and ultimately, immune suppression may contribute to increased risk for HAIs.
Defensins are small cationic, amphiphilic, cysteine-rich peptides produced by certain leukocytes and epithelial cells and comprise the front line of innate immune defense against pathogens [9–11]. Among them, α-defensins 1–3, also called human neutrophil peptides 1–3 (HNP1–3), are mainly expressed in neutrophils with antimicrobial activity against gram-negative and gram-positive bacteria, fungi, and viruses [12, 13]. Besides directly killing pathogens, HNP1–3 also facilitate the activation of adaptive immunity through chemoattracting naive T cells, immature dendritic cells, and monocytes to sites of inflammation [11, 14]. Therefore, HNP1–3 play an important role in the occurrence and development of infections.
DEFA1 and DEFA3, genes that encode HNP1–3, differ by only a single nonsynonymous coding variant within the third exon and are arrayed in a tandem but slightly random pattern of repeats on chromosome 8p23.1, displaying wide-ranging copy number variations (CNVs) [15, 16]. CNVs are defined as deletions, insertions, or duplications of a region of DNA 1 kilobase or larger in length and have significant impacts on genetic variation in the human genome by altering gene dosage, disrupting coding sequences, or perturbing long-range gene regulation [17]. DEFA1/DEFA3 copy number is reportedly correlated with protein levels of HNP1–3 in neutrophils...